Update on disease pathogenesis,diagnosis, and management of primary Sjögren’s syndrome

Primary Sjögren's syndrome (pSS) is a typical multisystem disease, characterized by lymphocytic infiltration of the exocrine glands leading to glandular dysfunction. Multiple systemic manifestations occur in those of serious conditions, with different courses and outcomes. Its pathogenesis is complex, and its diagnosis and management are being constantly updated and improved. We have failed to have much progress in targeted immunotherapy for pSS, and as yet this is still based on empirical treatment. Many studies have tried to define pSS more accurately, to study its pathogenesis, to find effective treatment strategies, opening up new avenues for early diagnosis and precise management of pSS.     

Adult T-biphenotypic acute leukaemia: clinical and biological features and outcome

Biphenotypic acute leukaemia with T-lymphoid and myeloid markers is rare and poorly documented. In the Leucemie Aigue Lymphoblastique de l'Adulte (LALA) prospective trial (LALA 94) of treatment for adult acute lymphoblastic leukaemia (ALL), seven patients (0.86%) had T-biphenotypic forms. The clinical and biological characteristics and outcome of these seven patients are reported here. The patients' median age was 35 years. At diagnosis, all had a tumoural syndrome and five had a mediastinal mass. In all the cases, leukaemic cells expressed myeloid and lymphoid markers. Two patients (28%) entered complete remission (CR) after induction chemotherapy. Four of the five remaining and assessable patients entered CR after designed salvage chemotherapy with mitoxantrone and high-dose cytosine arabinoside. Three patients are currently in CR. Three patients died, from treatment toxicity in two cases and progressive disease in one case. One patient relapsed 6 months after allogeneic bone marrow transplantation and is still alive. Thus, biphenotypic T-acute leukaemia is clinically frequently associated with mediastinal involvement and the response to conventional chemotherapy used in ALL is poor. However, sustained CR can be achieved by salvage chemotherapy combining an intercalating agent with high-dose cytosine arabinoside, as used in acute myeloid leukaemia.     

Congenital lobar emphysema: evaluation and long-term follow-up of thirty cases at a single center

Congenital lobar emphysema (CLE) is characterized by overdistension and air-trapping in the affected lobe, and is one of the causes of infantile respiratory distress. In this report, we review our 27 years of experience with 30 CLE patients. Patients' medical records were evaluated with regard to age, clinical presentation, diagnostic methods, associated diseases, treatment, histopathologic findings, and final clinical and laboratory findings at the end of a long-term period. The mean age of 30 patients (18 male) at diagnosis was 4.9 +/- 6.7 months (range, 2 days-2.5 years). Tachypnea, dyspnea, cough, cyanosis, wheezing, hoarseness, and decreased breath sounds on the affected side were the main symptoms and clinical findings. On chest X-rays, emphysema was seen in all patients; shift/herniation to the opposite lung, atelectasis, and pneumothorax were observed in 16, 5, and 2 cases, respectively. Computerized tomography of the thorax was performed in 16 cases and revealed emphysema at affected lobe/lobes in all, a shift/herniation to the opposite side in 12 cases, and atelectasis of neighbor lobe/lobes in 7 cases. All 8 patients who had perfusion scintigraphy showed reduced perfusion in the affected lobe. Narrowed and flaccid bronchi were detected in one patient by using flexible bronchoscopy. Blood gas analysis was performed in 11 patients, and hypoxia and hypercarbia were revealed in 9 and 7 of these patients, respectively. The most common affected lobe was the left upper lobe (57%), followed by the right upper lobe (30%) and right middle lobe (27%). Two lobes were involved in 4 patients. Associated abnormalities were observed in 5 patients. Twenty-one patients underwent lobectomy; 9 were followed conservatively. Ages at diagnosis were significantly younger in surgically treated patients. Emphysema was detected in all pathological specimens, with an additional bronchial cartilage deficiency in 2 patients. In the surgically treated group, 2 patients died and 2 patients were lost to follow-up. In the conservatively treated group, one patient was lost to follow-up. Mean follow-up duration of all patients was 63.2 +/- 56.2 months (range, 1-209 months). At follow-up visits, all patients were doing well. In surgically treated patients, chest X-rays were normal (9 cases), or showed hyperlucency on the operated side (6 cases) or chronic changes in the operation area (2 cases). Hyperexpansion in the affected lobe was found to be reduced in all cases in the conservatively treated group.     

The role of survivin in diagnosis, prognosis and treatment of breast cancer

Survivin is a cancer gene that is silenced in differentiated tissues, while overexpressed at high levels in vast majority of tumors. It has garnered great interests in recent years. Some essential properties characterizing it as an ideal target involve inhibiting apoptosis, promoting mitosis, stimulating vessel growth thus inducing chemo-resistance. These functions touch the full gamut of tumorigenesis, including proliferation, migration, and invasion, and collectively facilitate malignant behavior. In the case of breast cancer, survivin detection independent or combined in serum and/or urine has emerged as a measure for diagnosis. Moreover, many studies indicated aberrant expression of survivin is associated with poor prognosis and drug/radiation resistance. Strategies targeting survivin to treat breast cancer have got promising initial results. In this review, we summarize its role in breast cancer's diagnosis, prognosis, and treatment, with the intention to explain why this interesting molecule plays a conflicting role.     

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition. Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction<30%, pseudonormal or restrictive mitral inflow pattern at Doppler-echocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance<300 m or a peak oxygen uptake<12-14 ml/kg/min; 5) history of >1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.     

老年急性白血病340例临床分析

目的分析老年急性白血病的分布及预后情况。方法选取2009年9月至2013年5月在我院未经治疗的、年龄大于60岁的急性白病患者340例,对其发病年龄、预后危险因素、治疗、生存时间等指标进行分析。结果340例60岁以上老年急性白血病患者中,中位发病年龄68岁,急性淋巴细胞白血病（ALL）24例（7.06%）;在急性髓细胞白血病（AML）314例中,初发AML（de novo AML）250例（79.62%）。急性早幼粒细胞白血病（APL）仅9例。初发AML （非APL）中细胞遗传学和分子生物学预后较好的34例（14.11%）,预后差的61例（25.31%）,随着年龄增加,预后较好的比例降低,而预后差的比例升高。在有生存资料的患者93例中,85例选择了化疗。年龄也对完全缓解（CR）率、总体生存有显著影响。化疗后获得CR的患者生存明显优于未获得CR的患者。结论老年急性白血病患者预后差,如何提高总体生存仍然是一个难题。     

肺肉瘤样癌2例并文献复习

目的提高对肺肉瘤样癌（lung sarcomatoid carcinoma,LSC）的诊断、治疗及预后方面的认识。方法通过对2例LSC患者的诊治进行分析,结合相关文献复习。结果患者表现为咳嗽、咯血、胸痛,其症状与其它类型肺癌相似,增强CT示环形强化为其特征。肺组织活检确诊肺肉瘤样癌（病理及免疫组化）。手术联合化/放疗可延长患者生存时间。结论肺肉瘤样癌罕见,较一般肺癌更具侵袭性,预后差。本病缺乏特异性临床表征,增强CT扫描示环形强化为其特征,但诊断主要依靠手术病理。手术是LSC的首选治疗方法。     

The 6‐ and 12‐Month Outcomes of Older Medical Inpatients Who Recover from Subsyndromal Delirium

OBJECTIVES: To compare the 6‐ and 12‐month outcomes of patients who recovered from subsyndromal delirium (SSD) by 8 weeks with the outcomes of patients who did not recover or did not have an index episode. DESIGN: Secondary analysis of data collected for a cohort study of the prognosis of delirium. SETTING: University‐affiliated primary acute care hospital. PARTICIPANTS: Older medical inpatients with prevalent, incident, or no SSD were classified into three mutually exclusive groups at 8 weeks (SSD‐recovered, SSD‐not recovered, no SSD) and followed up at 6 and 12 months. MEASUREMENTS: The primary hierarchical composite outcome was death, institutionalization, or cognitive or functional decline at 6 and 12 months. In secondary analyses, components of the primary outcome were examined separately. RESULTS: Of the 129 patients assessed at 8 weeks, 51, 47, and 31 met criteria for SSD‐recovered, SSD‐not recovered and no SSD, respectively. At 6 and 12 months, the primary and secondary outcomes of the SSD‐recovered group were better than the outcomes of the SSD‐not recovered group and, for the most part, intermediate between the outcomes of the SSD‐not recovered and no SSD groups. CONCLUSION: Recovery from SSD appears to predict better longer‐term outcomes than no recovery. Efforts to identify and treat SSD in older medical inpatients may improve outcomes.     

Retrospective analysis of hepatic perivascular epithelioid cell tumour (PEComa) in a single centre for clinical diagnosis and treatment clinical diagnosis and treatment of hepatic PEComa

Our primary objective was to investigate the clinical features, diagnosis, treatment and prognosis of hepatic perivascular epithelioid cell tumour (PEComa).Thirty-five cases of pathologically proven hepatic PEComa that were treated in the Department of Hepatobiliary Centre of the First Affiliated Hospital of Nanjing Medical University from January 2008 to February 2019 were retrospectively analysed, and the literature was also reviewed.Twenty-nine females and 6 males were included in this study. The mean age of these patients was 48.0 years (range, 21–75 years). Thirteen patients complained of upper abdominal pain or discomfort, while others were accidentally discovered by imaging examination. Hepatic PEComas tended to occur in the right lobe of the liver (20 cases in the right lobe, 13 in the left lobe and 2 in the caudate lobe). Two cases were characterized by multiple tumours, and the remaining cases were single lesions (range, 1.2–12 cm). Only 8 cases were correctly diagnosed by the preoperative imaging examination, and the correct diagnosis rate was only 22.9%. The postoperative immunohistochemistry analysis showed that hepatic PEComas are positive for human melanoma black 45, Melan-A and smooth muscle actin, with the exception of 1 case that was negative for Melan-A. All patients undergoing an operation accepted regular follow-up, and the average time was 66.5 months (range, 3–132 months). Two patients who experienced tumour recurrence and 1 patient who died of cardiovascular disease, but the remaining patients showed no evidence of tumour recurrence or metastasis during the follow-up period.Hepatic PEComas are a rare type of tumours that mainly occur in young and middle-aged women. The lack of clinical manifestations and imaging findings increases the difficulty of determining a preoperative diagnosis, which mainly depends on the results of pathological examinations. Surgery is currently the only effective treatment, and long-term clinical follow-up is necessary due to the aggressive behaviour and relapse of hepatic PEComa in some patients.     

The impact of age on the diagnosis and therapy of myelodysplastic syndromes: results from a retrospective multicenter analysis in Germany

Myelodysplastic syndromes (MDS) is a disease of predominantly elderly patients with a median age of >70 yrs. However, data on the management of these patients outside of clinical trials are scarce. To assess patterns of MDS management in routine patient care with regard to the impact of age, we conducted a multicenter, representative survey of MDS health services in Germany. Data of 269 patients treated at 57 institutions were collected from preplanned chart reviews and were analyzed retrospectively. At diagnosis, median age was 70 yrs, 50% of patients had a Karnofsky index (KI) of 90%, and 12% had a comorbidity index ≥ 3 according to Sorror et al. (J Clin Oncol, 25, 2007, 4246). Cytogenetic analysis and International Prognostic Scoring System (IPSS) risk assessment were performed significantly less frequently in patients >75 yrs than in patients ≤75 yrs (P < 0.001 and P = 0.019). In bivariate analysis, potential predictors for performing IPSS risk assessment were age ≤75 yrs (y/n, P = 0.019), diagnosis at a university hospital (y/n, P = 0.001), WHO subtypes RCUD (y/n, P = 0.028), RARS (y/n, P = 0.002), or RAEB II (y/n, P = 0.037). Patients ≤75 yrs were more likely to receive active therapies (i.e., chemotherapy, immunomodulatory therapy, or epigenetic therapy) than patients >75 yrs (51% vs. 37%, P = 0.007). In bivariate analysis age ≤75 yrs (y/n, P = 0.007) was a significant predictor for active treatment with no correlation with the other predictors [IPSS risk score int‐2 or high (y/n, P = 0.005), WHO subtypes RCUD (y/n, P < 0.001), RCMD (y/n, P = 0.003), RAEB II (y/n, P < 0.001), or CMML I (y/n, P = 0.020)]. This survey confirms the impact of age on the thoroughness of MDS diagnosis and the decision for active treatment. As cytogenetic analysis and risk assessment are essential for the choice of appropriate therapy, elderly patients in particular may not be receiving adequate treatment.     

肾上腺皮质腺癌的诊断与治疗

目的 总结肾上腺皮质腺癌（ACC）的诊治经验,提高肾上腺皮质癌的诊治水平.方法 对5例ACC患者的临床表现、实验室及影像学检查、治疗和预后进行回顾性分析.结果 本组B超示肾上腺实质性中等回声,内部回声不均匀,可见点状血流反射;CT均示肿瘤边缘模糊,CT值32 ～ 65 HU,强化不均匀;MRI示肿瘤边界欠清,T2加权片上2例呈高信号,1例呈高低混杂信号,病灶中心坏死区无明显强化.5例均行开放性手术完全切除肿物,术后应用米托坦2例、放疗1例;术后随访6 ～ 36个月,平均生存23个月.结论 B超、CT等检查有利于ACC的早期诊断,手术切除是治疗ACC的有效方法.     

Natural history and clinical outcomes of pancreatic neuroendocrine neoplasms based on the WHO 2017 classification; a single-center experience of 30 years

Background/ObjectivesThis single-center study aimed to evaluate treatment outcomes and long-term prognosis of patients with pancreatic neuroendocrine neoplasms (PanNENs) based on the World Health Organization (WHO) 2017 classification.MethodsWe enrolled 245 patients with PanNENs treated at Kyushu University Hospital between January 1987 and March 2018. PanNENs were categorized according to the WHO 2017 classification or further subdivisions of Ki-67 index. Clinicopathological features, median survival time (MST), and prognostic factors were retrospectively analyzed.ResultsThe number of PanNENs, especially non-functioning PanNENs, has increased over the last decade. The mean MST of all patients was 202 months; which was longest in patients with NET G1 (n = 145, MST = 261 months) relative to NET G2 (n = 72, 132 months), NET G3 (n = 3, 34 months) and NEC G3 (n = 17, 9 months). Prognosis in patients with surgery as the first-line treatment was significantly better than in those with drug therapy. However, 26% of patients who underwent curative resection developed recurrence after a median time of 28.7 months. In unresectable PanNENs (n = 97), the MST and 5-year survival rate were 78 months and 55.8%, respectively. Poor differentiation, Ki-67 index of >10% and presence of liver metastasis were significant unfavorable predictors. Response to first-line therapy (stable disease/partial response) and three or more treatment regimens were significant favorable predictors for unresectable PanNENs according to multivariate analyses (p < 0.01).ConclusionsWe demonstrated the utility of the WHO 2017 classification for PanNENs in the real clinical setting. For better prognosis in PanNENs, the use of three or more regimens should be considered.     

Differentiating chronic lymphocytic leukemia from monoclonal B-lymphocytosis according to clinical outcome: on behalf of the GIMEMA chronic lymphoproliferative diseases working group

Background

Optimal lymphocyte parameters and thresholds for the diagnosis of chronic lymphocytic leukemia have been proposed by The National Cancer Institute sponsored Working Group and recently updated by the International Workshop on chronic lymphocytic leukemia. However, it is not clear how these criteria apply to patient management in daily clinical practice and whether the lymphocyte thresholds recommended truly predict clinical outcome in early chronic lymphocytic leukemia.

Design and Methods

For the purpose of this study, an observational database of the GIMEMA (Gruppo Italiano Malattie Ematologiche dell’Adulto) which included 1,158 patients with newly diagnosed Binet stage A chronic lymphocytic leukemia who were observed at different primary hematology centers during the period 1991–2000, was used.

Results

Among 818 consecutive chronic lymphocytic leukemia patients with Rai stage 0 (i.e. no palpable lymphadenopathy or hepatosplenomegaly) who had flow cytometry evaluations at the time of diagnosis and were included in a GIMEMA database, both absolute lymphocyte count and B-cell count were of a similar value in predicting time to first treatment as continuous variables (P<0.0001). Receiver operating characteristic analysis identified an absolute lymphocyte count of 11.5×10⁹/L and an absolute B-cell count of 10.0×10⁹/L as the best thresholds capable of identifying patients who will require treatment from those with stable disease. However, in a Cox’s multivariate analysis only the B-cell count retained its discriminating power (P<0.0001) and the estimated rate of progression to chronic lymphocytic leukemia requiring treatment among subjects with a B-cell count less than 10.0×10⁹/L was approximately 2.3% per year (95% CI 2.1–2.5%) while it was 2-fold higher for patients with a B-cell count of 10.0×10⁹/L or over (i.e. 5.2% per year; 95% CI 4.9–5.5%). Finally, in this community-based patient cohort, the B-cell threshold defined by investigators at the Mayo Clinic (i.e. 11.0×10⁹/L) allowed patients to be divided into two subsets with a higher and lower likelihood of treatment (P<0.0001).

Conclusions

Our results, based on a retrospective patients’ cohort, provide a clear justification to retain the B-cell count as the reference gold standard of chronic lymphocytic leukemia diagnosis and imply that a count of 10×10⁹/L B cells is the best lymphocyte threshold to predict time to first treatment. The use of clinical outcome to distinguish chronic lymphocytic leukemia from other premalignant conditions, such as monoclonal B-cell lymphocytosis, is a pragmatic approach meeting the patients’ need to minimize the psychological discomfort of receiving a diagnosis of leukemia when the risk of adverse clinical consequences is low.     

Chemokines in pathology and medicine

About 50 human chemokines and nearly 20 receptors have been identified and characterized in little more than a decade since the discovery of interleukin 8 (IL-8), the first chemotactic cytokine. Research in this field has dramatically changed our understanding of leucocyte traffic in inflammation and immunity. This paper has been written for scientists and practitioners in the field of medicine. It reviews in concise and intelligible form information that I consider useful for understanding the role of chemokines in human pathophysiology. The main areas covered are: (i) the basics of chemokine structures, mode of action, activities and selectivity; (ii) newer aspects of the broad involvement of chemokines in the regulation of immune defence and the housekeeping of the immune system; (iii) the role of chemokines in pathology as illustrated by animal models and studies of human diseases; and (iv) novel therapeutic approaches for a variety of inflammatory conditions, which are based on modulation of chemokine activity.     

Incidence of ‘Dry Tap’ on Bone Marrow Aspirations in Lymphomas and Carcinomas

Of 2 907 bone marrow aspirations in patients with various malignancies, 192 or 6.6 % exhibited ‘dry tap’. In about 80 % of the ‘dry tap’ there was material present inside the bone marrow needle which gave smears useful for evaluation of the bone marrow cytology. About 23 % displayed normal cytology. Bone marrow involvement could be diagnosed in 13 out of 55 ‘dry tap’ in Hodgkin's disease, 41 out of 46 in chronic lymphocytic leukaemia and lymphosarcoma, 6 out of 20 in reticulum cell sarcoma, 6 out of 9 in myelomatosis and 20 out of 45 in carcinoma. In a material of 174 aspirations with tumour cells in the bone marrow aspirate, the highest incidence of ‘dry tap’ was found in patients with Hodgkin's disease and patients with carcinoma, the lowest incidence in patients with multiple myeloma.